This project, since its inception, has represented an effort to integrate the distinctive experimental approaches of several laboratories in the study of the interrelationship of the neoplastic process and immune recognition. The program has two interrelated themes: (1)\the understanding of normal-versus-neoplastic cell development; and (2)\the expression of cell surface differentiation and tumor-associated antigens and their recognition by elements of the immune system. The expression of proteins encoded by the entire set of known oncogenes will be evaluated by Dr. Lerner in Project II. The availability of polyclonal and monoclonal antibodies to predetermined peptides of these proteins will enable Dr. Lloyd Old, who will collaborate on this project, to include his entire bank of normal and neoplastic human tissues in this crucial screen. Dr. Sherman in Project IV and Dr. Sprent in Project V, respectively, will study the normal development of murine T and B cells. Dr. Sherman has already provided the first studies of neonatal and adult CTL repertoires. She now plans to assess the relative roles of the thymus and periphery in the establishment of the mature CTL repertoire. In a similar vein, Dr. Sprent in Project V will assess B-cell development and, in particular, will evaluate environmental influences in the life cycle of various B-cell subpopulations. In Project III, Dr. Klinman will attempt to extend his previous demonstrations that B cells, like T cells, can detect non-self cell surface antigens, as they are expressed in the context of self MHC antigens. The studies of Dr. Bevan in Project I should provide a direct approach to furthering our understanding of T-cell recognition by the analysis of the T-cell receptor at the genetic and cellular level. Independent studies from a number of laboratories, including Dr. Bevan's, in the past year hold the promise for the resolution of the T-cell receptor dilemma in the near future. Overall, we believe this program represents a highly integrated approach to many of the fundamental issues of lymphoid cell development, immune recognition, and the neoplastic process. (LB)